Alternative methods for the treatment of post-menopausal troubles.

BACKGROUND: Menopause is described as the transition from the reproductive phase of a women to the non reproductive. Changes in hormone levels might lead to complaints and health consequences especially during peri- and postmenopause. Hormone therapy has a potential damaging health risk profile and is recommended for temporal limited therapy for acute vasomotor symptoms only.
OBJECTIVE: The present HTA-report aims to assess the effectiveness and the cost-effectiveness of alternative treatment methods for women with postmenopausal symptoms in Germany regarding patient relevant endpoints (reduction of symptoms and frequency of adverse events and improvement of quality of life).
METHODS: A systematic literature search was carried out in 33 relevant databases in September 2010. Citations were selected according to pre-defined criteria and were extracted and evaluated.
RESULTS: In the systematic research 22 studies are identified for the effectiveness evaluation, 22 primary studies and one review. High doses of isolated genistein reduce the frequency/intensity of hot flashes while low doses of genistein show no significant effect. Intake of isoflavone extract such as genistein, daidzein, glycitein in various combinations does not have an effect on improvement of cognitive function or vaginal dryness. The effect of black cohosh and hop extract for menopausal complaints cannot be determined since results are heterogenous. The combination of isoflavone, black cohosh, monk's pepper, valerian and vitamin E has a positive effect on menopause symptoms. Ginkgo biloba shows no significant effect on menopause symptoms and cognitive improvement beside mental flexibility. Acupuncture has a significant influence on hot flashes especially in severe cases. DISCUSSION/
CONCLUSION: No final statement can be drawn regarding the effectiveness of alternative treatment methods due to qualitative shortcomings of included studies and a general limited availability of studies in this field. Furthermore, the generalization of the present HTA is limited due to the inclusion of only postmenopausal women.

Summary

Health policy background

Menopausal symptoms are common in menopause, a phase describing the transition from the reproductive to the non-reproductive phase in a woman’s life. Key event is the last menstruation which occurs in Germany on average at age 51 years. Approximately 18 Millionen postmenopausal women in the age group 50 and above live in Germany.

Hormonal changes cause menopausal symptoms which may result in a decreased quality of life. Hormone therapy (estrogen/progestogen combination products) is one, but temporally limited option due to increased health risks (growing risk of breast cancer, pulmonary embolism, and dementia). At the same time, there is increasing interest and need for alternative treatment methods including phytotherapeutics. However, the evidence is limited with regard to the effectiveness, the clinical use and the costs of alternative treatment methods.

Scientific background

Menopausal transition is a natural part of a woman’s life, describing the transition from the reproductive to the non-reproductive phase. This period starts between age of 40 and 50 and is characterized by the reduction of estrogen levels (female hormones). Key event is the last menstruation. The hormonal conversion, especially the lack of estrogens, leads to moderate or severe menopausal symptoms (ICD-10 code N95. Climacteric disturbances) in two thirds of women. These menopausal symptoms are not life-threatening, but may reduce quality of life considerably. Main complaints are vasomotor and vaginal symptoms, accompanied by heart complaints, depressive episodes and sleep problems.

Hormone therapy as one effective treatment option is recommended in Germany only for temporal use due to its potential health risks (increased risk for breast cancer, cardiovascular diseases, dementia).

Use of hormone therapy decreased by 64 % between 1999 and 2007, but costs for therapies and medical prescriptions still amount to up to 296 Millionen Euro for the Statutory Health Insurance (Gesetzliche Krankenversicherung (GKV)). German guidelines lack alternatives to hormone therapy so far. Nonetheless, about 15 to 17 % of postmenopausal women with menopausal symptoms – influenced by ethnicity, education and medical consultation – use alternative treatment methods (e. g. natural products, mind-body-therapies, acupuncture). Phytotherapeutics (drugs made out of plants, e. g. lineseeds, red clover, St. John’s wort, hop or black cohosh) are most frequently used as tea, through nutrition oder as food supplements. Costs for alternative treatment methods are not or only partially reimbursed. Normally, the patient pays the costs.

Research questions

The aim of the present Health Technology Assessment (HTA) is to assess the effectiveness and cost-effectiveness of alternative therapeutic methods for menopausal symptoms in postmenopausal women in Germany.

Study questions regarding the clinical effectiveness are:

What is the effectiveness of alternative methods of treatment compared to no treatment in all women with postmenopausal symptoms?

Are there variations in the effectiveness of different alternative methods of treatments of postmenopausal symptoms?

What is the effectiveness of alternative methods of treatment of postmenopausal symptoms compared to hormone therapy?

What is the effectiveness of alternative treatment methods for the improvement of health-related quality of life in postmenopausal symptoms compared to no treatment at all?

Economic, ethical, social and legal aspects with respect to the use of alternative methods of treatment are addressed additionally.

Methods

In September 2010, a systematic literature search was performed in 33 relevant databases. The identified citations are selected according to pre-defined criteria by two independent reviewers using methods of evidence-based medicine. Literature from previous five years is included and publication language is not considered a limitation.

Results

22 studies fulfill the inclusion criteria (15 studies with use of phytotherapy, six with acupuncture and one systematic review). Most studies evaluate isoflavone-containing substances, two studies assess the effectiveness of black cohosh (cimicifuga racemosa), one study the effect of ginkgo, and two other studies assess the effectiveness of hop extract. Four acupuncture studies show results from the Acupuncture on hot flush among menopausal women (ACUFLASH)-study; the other two studies are from the same study too. Therefore, results are summarized and reported. All studies about isoflavone-containing (e. g. Daidzein, Genistein, red clover) and other phythotherapeutics are randomized controlled trials, six studies have a cross-over-design.

Endpoints are changes of quality of life, strengths and intensity of hot flush, cognitive changes, anxiety and depression. Adverse events are measured in six studies.

Two studies and one systematic review give evidence that high-dose isolated Genistein might reduce hot flush, whereas no effect was seen with low-dose genistein. Studies with Isoflavone combining Genistein, Daidzein, Glycetein do not show a significant effect on cognitive capability or vaginal dryness. Study results concerning black cohosh and hop extracts are heterogeneous, therefore, no conclusive evidence can be found. One study gives evidence that the combination of Isoflavones with black cohosh, hemp tree, valerian and vitamin E shows an improvement of postmenopausal symptoms. In one study Ginkgo bilboa has no significant effect on postmenopausal symptoms beside mental flexibility. Two studies report a significant improvement in hot flushes, especially in severity of hot flushes.

No study was identified to evaluate the effectiveness of alternative treatment methods compared to hormone therapy. Therefore, no scientific assessment is possible.

One systematic review is identified assessing the effectiveness of soya isoflavone extracts depending on the genistein content in the treatment of hot flushes. None of the included studies in the review was included as primary study, as all studies were published between 2003 and 2004 and are thus out of the period included of the present HTA.

No studies are identified which address economic, ethical, social oder legal aspects of alternative treatment methods or possible consequences of the absent funding by GKV and its possible impact of alternative treatment methods.

Discussion

Menopausal symptoms are highly prevalent and due to their potential restriction in the quality of life a relevant healthcare policy and medical topic. Considering the fact that hormone preparations are only of limited temporal use, there is great uncertainty among respective patients as well as need and growing interest in alternative treatment methods.

All included RCT show multiple shortcomings in quality with regard to concealment/randomisation, sample size calculation and blinding, which led to the down-grading of the evidence level of some studies by the authors of the present HTA.

A considerable weakness of the present HTA is the restriction to postmenopausal women only. This decision was based on financial and personal resources. Studies show a high therapeutic need of alternative treatment methods especially in pre- and perimenopausal women because symptoms decrease with aging. The generalizability of the present HTA is reduced by excluding pre- and perimenopausal women.

Comparability between studies is limited due to inclusion of different alternative treatment methods, different end points and scales. A general statement regarding the effectiveness of alternative treatment methods cannot be drawn. Further alternative treatment methods (e. g. relaxation techniques) were identified in the literature search, but did not fulfill the inclusion criteria of the present HTA.

Conclusions/Recommendations

The provision of alternative treatment methods in menopausal symptoms are relevant because the frequency of menopausal symptoms which can result in a reduction of life quality and the widespread use of alternative treatments despite missing data on their efficacy and safety.

No general statement about the effectiveness of isoflavones and acupuncture in the treatment of menopausal symptoms can be made due to the heterogeneity of the included studies and the generally limited number of studies.

Additionally, the German Office of Consumer Protection and Food Safety stated that the consumption of isolated or enriched isoflavones are with low probability a health risk.

Further research including high quality studies is needed regarding the high interest in alternative therapeutic methods in women with menopausal symptoms.